(a) Field of the Invention
A novel use of an extract of Lycoris chejuensis or a compound isolated therefrom for inhibition of β-amyloid production and/or prevention, improvement and/or treatment of a neurodegenerative disease is provided. More specifically, an inhibitor against β-amyloid production, and/or a composition for prevention and/or treatment of a neurodegenerative disease, containing one or more selected from the group consisting of an extract of Lycoris chejuensis, dihydrolycoricidine, 2-methoxypancracine, lycoricidine, and lycoricidinol, as an active ingredient; a method of inhibiting β-amyloid production, and/or preventing and/or treating a neurodegenerative disease, using the same; and, a method for preparing the same, are provided.
(b) Description of the Related Art
Dementia which is one of representative neurodegenerative diseases refers to symptoms characterized by deterioration of normal brain functions including intelligence such as memory, cognition, comprehension, computation abilities, learning skills, language abilities, judgment, and the like, due to brain cell damage caused by various reasons. Senile dementia which is age-related mental disorder resulted from degenerative change of brain mainly occurs in old age from about 65 to 70 years old.
Alzheimer's disease becomes most important senile dementia, and has been known to be mainly caused by accumulation of β-amyloid in brain and neurotoxicity resulted therefrom. In particular, β-amyloid forms plaque in which proteins are accumulated and aggregated in brain, causes Alzheimer's disease. The Alzheimer's disease exhibits pathohistological characteristics such as overall brain atrophy, cerebral ventricular expansion, neurofibrillary tangle, senile plaque, and the like, decreased intellectual functions including memory, judgment and language skills, and the like, and behavior disorders, and it may be involved with psychiatric symptoms such as depression. In addition, the above symptoms may be gradually advanced to lead death 6 to 8 years after attack of disease.
β-amyloid is known to be produced from amyloid precursor protein(APP) by continuous actions of membrane protein hydrolytic enzymes, β-secretase(BACE1) and γ-secretase. β-amyloid is largely classified into 2 types, Aβ40 and Aβ42, each of which consists of 40 or 42 amino acids. Although most of β-amyloid is Aβ40, relatively less formed Aβ42 easily makes plaque, and thus, it has been designated as a most important causative agent.
Tacrine (Cognex, 1994) and donepezil (Aricept, 1996), which are FDA approved drugs, have been used as representative anti-dementia drugs. The mechanisms of these drugs are known to increase neurotransmitter acetylcholine by inhibiting the activity of acetylcholine esterase (AChE), which is hydrolytic enzyme of acetylcholine that plays an important part in the central nervous pathway, thereby preventing and treating dementia. However, tacrine is expensive compared to the efficacy and may cause serious hepatotoxicity, and donepezil may stimulate parasympathetic nerves to cause various side effects such as vomiting, nausea, diarrhea, etc. In addition, these drugs are not for fundamental treatment such as improvement of brain disease, but only for alleviation of main symptoms of dementia such as memory impairment.
Therefore, studies on the development of novel anti-dementia drugs capable of fundamental treatment without side effects have been actively under progress. One approach is to develop material capable of blocking production of β-amyloid which is known to be a causative agent for Alzheimer's disease, but effective therapeutic agent has not been developed yet.
Meanwhile, dihydrolycoricidine, which is mainly contained in Hymenocallis littoralis, Hymenocallis latifolia, and the like, has been known to exhibit anti-virus and anti-cancer effects, but it has not been reported to exhibit dementia prevention and treatment effects.
2-methoxypancracine, which is contained in Hymenocallis sp., has been known to exhibit anti-inflammatory, antioxidant, and antibacterial effects, but it has not been reported to exhibit dementia prevention and treatment effects.
In addition, lycoricidine and lycoricidinol, which are contained in Narcissus sp., Lycoris sp., Pancratium sp., Haemanthus sp., and the like, have been known to exhibit anti-viral and anticancer effects (Gabrielsen, B. et al. J. Nat. Prod. 55: 1569, 1992, Mondon, A. et al. Chem. Ber. 108: 445, 1975), but they have not been reported to exhibit β-amyloid production inhibiting effects or dementia prevention and treatment effects.
Meanwhile, Lycoris chejuensis, which is a white plant belonging to Amaryllidaceae and distributed only in Cheju, South Korea, has been recently named (Tae and Ko, Kor. J. Pl. Tax. 23: 233, 1993). However, there have been insufficient studies on chemical analysis or physiological activity and clinical effects thereof.